Summary: Core C Pathology The goal of this Neuropathology (NP) Core is to serve the 4 Projects described in this proposal, which will study different aspects of the transformation of A peptides, tau, and the prion protein (PrP) from normal proteins/peptides to soluble abnormal proteins/peptides and to insoluble amyloid fibrils, or in the case of tau, to neurofibrillary tangles (NFTs). Projects 2, 3, and 4 will largely study the progression of proteins/peptides in vitro, while Project 1 will study the progression in a variety of transgenic (Tg) mice and rats. The NP Core's goal is to apply standard neurohistopathological and immunohistological techniques to the brains of animals used by the Projects, in order to visualize the subcellular neuronal compartments that are targeted and the morphology of neurons and glia. We have a large number of mouse and rabbit antibodies specific for different transitional forms of A peptides, tau, and PrP as well as antibodies that will identify specific subcellular compartments. This global view of abnormal protein/peptide transitions in brain tissues will further our understanding of the molecular basis of disease progression.